| Record Information |
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| Version | 4.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2005-11-16 15:48:42 UTC |
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| Update Date | 2020-02-27 20:30:42 UTC |
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| HMDB ID | HMDB0000522 |
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| Secondary Accession Numbers | |
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| Metabolite Identification |
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| Common Name | 3-Methylglutaconic acid |
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| Description | 3-Methylglutaconic acid is an intermediate (as the CoA thioester) in the leucine degradative pathway as well as the mevalonate shunt, a pathway that links isoprenoid metabolism with mitochondrial acetyl-CoA metabolism (PMID: 7603789 ). 3-methylglutaconyl-CoA hydratase is involved in the metabolism process of 3-methylglutaconic acid. When present in sufficiently high levels, 3-methylglutaconic acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of 3-methylglutaconic acid are associated with at least five inborn errors of metabolism including 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methylglutaconic aciduria type I, 3-methylglutaconic aciduria type III, 3-methylglutaconic aciduria type IV, and guanidinoacetate methyltransferase deficiency (GAMT deficiency). 3-Methylglutaconic acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures. |
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| Structure | |
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| Synonyms | | Value | Source |
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| 3-Methylglutaconate | Generator | | b-Methylglutaconate | HMDB | | b-Methylglutaconic acid | HMDB | | beta-Methylglutaconate | HMDB | | beta-Methylglutaconic acid | HMDB | | Β-methylglutaconic acid | HMDB | | 3-Methyl-2-pentenedioic acid | HMDB | | 3E-Methylglutaconate | HMDB | | 3-Methylglutaconic acid | HMDB, MeSH |
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| Chemical Formula | C6H8O4 |
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| Average Molecular Weight | 144.1253 |
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| Monoisotopic Molecular Weight | 144.042258744 |
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| IUPAC Name | (2E)-3-methylpent-2-enedioic acid |
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| Traditional Name | β-methylglutaconic acid |
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| CAS Registry Number | 5746-90-7 |
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| SMILES | C\C(CC(O)=O)=C/C(O)=O |
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| InChI Identifier | InChI=1S/C6H8O4/c1-4(2-5(7)8)3-6(9)10/h2H,3H2,1H3,(H,7,8)(H,9,10)/b4-2+ |
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| InChI Key | WKRBKYFIJPGYQC-DUXPYHPUSA-N |
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| Chemical Taxonomy |
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| Description | belongs to the class of organic compounds known as methyl-branched fatty acids. These are fatty acids with an acyl chain that has a methyl branch. Usually, they are saturated and contain only one or more methyl group. However, branches other than methyl may be present. |
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| Kingdom | Organic compounds |
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| Super Class | Lipids and lipid-like molecules |
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| Class | Fatty Acyls |
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| Sub Class | Fatty acids and conjugates |
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| Direct Parent | Methyl-branched fatty acids |
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| Alternative Parents | |
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| Substituents | - Methyl-branched fatty acid
- Unsaturated fatty acid
- Dicarboxylic acid or derivatives
- Carboxylic acid
- Carboxylic acid derivative
- Organic oxygen compound
- Organic oxide
- Hydrocarbon derivative
- Organooxygen compound
- Carbonyl group
- Aliphatic acyclic compound
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | |
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| Ontology |
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| Physiological effect | Health effect: |
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| Disposition | Route of exposure: Source: Biological location: |
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| Process | Naturally occurring process: |
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| Role | Indirect biological role: Industrial application: Biological role: |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | Not Available | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| Disease References | | 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency |
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- Bischof F, Nagele T, Wanders RJ, Trefz FK, Melms A: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy. Ann Neurol. 2004 Nov;56(5):727-30. [PubMed:15505778 ]
- Santarelli F, Cassanello M, Enea A, Poma F, D'Onofrio V, Guala G, Garrone G, Puccinelli P, Caruso U, Porta F, Spada M: A neonatal case of 3-hydroxy-3-methylglutaric-coenzyme A lyase deficiency. Ital J Pediatr. 2013 May 24;39:33. doi: 10.1186/1824-7288-39-33. [PubMed:23705938 ]
- G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
| | 3-Methylglutaconic aciduria type I |
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- Engelke UF, Kremer B, Kluijtmans LA, van der Graaf M, Morava E, Loupatty FJ, Wanders RJ, Moskau D, Loss S, van den Bergh E, Wevers RA: NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism. NMR Biomed. 2006 Apr;19(2):271-8. [PubMed:16541463 ]
- Wortmann SB, Kremer BH, Graham A, Willemsen MA, Loupatty FJ, Hogg SL, Engelke UF, Kluijtmans LA, Wanders RJ, Illsinger S, Wilcken B, Cruysberg JR, Das AM, Morava E, Wevers RA: 3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy. Neurology. 2010 Sep 21;75(12):1079-83. doi: 10.1212/WNL.0b013e3181f39a8a. [PubMed:20855850 ]
- G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
| | Eosinophilic esophagitis |
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- (). Mordechai, Hien, and David S. Wishart. .
| | 3-methylglutaconic aciduria type II, X-linked |
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- Cantlay AM, Shokrollahi K, Allen JT, Lunt PW, Newbury-Ecob RA, Steward CG: Genetic analysis of the G4.5 gene in families with suspected Barth syndrome. J Pediatr. 1999 Sep;135(3):311-5. [PubMed:10484795 ]
| | 3-Methylglutaconic Aciduria type VI |
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- Wortmann S, Rodenburg RJ, Huizing M, Loupatty FJ, de Koning T, Kluijtmans LA, Engelke U, Wevers R, Smeitink JA, Morava E: Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. Mol Genet Metab. 2006 May;88(1):47-52. doi: 10.1016/j.ymgme.2006.01.013. Epub 2006 Mar 9. [PubMed:16527507 ]
| | 3-Methylglutaconic Aciduria type IV |
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- Wortmann SB, Rodenburg RJ, Jonckheere A, de Vries MC, Huizing M, Heldt K, van den Heuvel LP, Wendel U, Kluijtmans LA, Engelke UF, Wevers RA, Smeitink JA, Morava E: Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy. Brain. 2009 Jan;132(Pt 1):136-46. doi: 10.1093/brain/awn296. Epub 2008 Nov 16. [PubMed:19015156 ]
| | 3-Methylglutaconic Aciduria type V |
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- Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T: New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies. Pediatr Res. 2012 Oct;72(4):432-7. doi: 10.1038/pr.2012.92. Epub 2012 Jul 13. [PubMed:22797137 ]
| | 3-Methylglutaconic aciduria type VII |
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- Wortmann SB, Zietkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lucke T, Ounap K, Zordania R, Yaplito-Lee J, van Bokhoven H, Spelbrink JN, Vaz FM, Pras-Raves M, Ploski R, Pronicka E, Klein C, Willemsen MA, de Brouwer AP, Prokisch H, Katsanis N, Wevers RA: CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet. 2015 Feb 5;96(2):245-57. doi: 10.1016/j.ajhg.2014.12.013. Epub 2015 Jan 15. [PubMed:25597510 ]
| | Sengers syndrome |
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- Di Rosa G, Deodato F, Loupatty FJ, Rizzo C, Carrozzo R, Santorelli FM, Boenzi S, D'Amico A, Tozzi G, Bertini E, Maiorana A, Wanders RJ, Dionisi-Vici C: Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria. J Inherit Metab Dis. 2006 Aug;29(4):546-50. doi: 10.1007/s10545-006-0279-y. Epub 2006 May 30. [PubMed:16736096 ]
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| General References | - Mitchell GA, Jakobs C, Gibson KM, Robert MF, Burlina A, Dionisi-Vici C, Dallaire L: Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. Prenat Diagn. 1995 Aug;15(8):725-9. [PubMed:7479590 ]
- Holme E, Greter J, Jacobson CE, Larsson NG, Lindstedt S, Nilsson KO, Oldfors A, Tulinius M: Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. Pediatr Res. 1992 Dec;32(6):731-5. [PubMed:1287564 ]
- Costeff H, Elpeleg O, Apter N, Divry P, Gadoth N: 3-Methylglutaconic aciduria in "optic atrophy plus". Ann Neurol. 1993 Jan;33(1):103-4. [PubMed:8494328 ]
- Sheffer RN, Zlotogora J, Elpeleg ON, Raz J, Ben-Ezra D: Behr's syndrome and 3-methylglutaconic aciduria. Am J Ophthalmol. 1992 Oct 15;114(4):494-7. [PubMed:1384336 ]
- Kelley RI: Quantification of 3-methylglutaconic acid in urine, plasma, and amniotic fluid by isotope-dilution gas chromatography/mass spectrometry. Clin Chim Acta. 1993 Nov 15;220(2):157-64. [PubMed:8111960 ]
- Kelley RI, Kratz L: 3-methylglutaconic acidemia in Smith-Lemli-Opitz syndrome. Pediatr Res. 1995 May;37(5):671-4. [PubMed:7603789 ]
- Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]
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